Charge neutral rhenium tricarbonyl complexes of tridentate N-heterocyclic carbene ligands that bind to amyloid plaques of Alzheimer's disease

Article abstract of DOI:10.1039/c9dt04687a

Two tridentate ligand systems bearing N-heterocyclic carbene (NHC), amine and carboxylate donor groups coupled to benzothiazole- or stilbene-based amyloid binding moieties were synthesised. Reaction of the imidazolium salt containing pro-ligands with Re(CO)₅Cl yielded the corresponding rhenium metal complexes which were characterised by NMR, and X-ray crystallography. These ligands are of interest for the potential preparation of technetium-99m imaging agents for Alzheimer's disease and the capacity of these rhenium complexes bind to amyloid fibrils composed of amyloid-β peptide and amyloid plaques in human frontal cortex brain tissue was evaluated using fluorescence microscopy. These studies show that the complexes bound efficiently to amyloid-β fibrils and some evidence of binding to amyloid-β plaques.

Full text of DOI:10.1039/c9dt04687a

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14 March 2017
Pages 3073-3412
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Charge Neutral Rhenium Tricarbonyl Complexes of Tridentate N-Heterocylic Carbene
View Article Online
DOI: 10.1039/C9DT04687A
Ligands that Bind to Amyloid Plaques of Alzheimer’s Disease
Nuchareenat Wiratpruk,a Asif Noor,b Catriona A. McLean,c Paul S. Donnelly and Peter J. Barnarda*
aDepartment of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe
University, Victoria, 3086, Australia.
bSchool of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of
Melbourne, Parkville, Victoria, 3010, Australia.
cFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria,
3010, Australia
Abstract
Two tridentate ligand systems bearing N-heterocyclic carbene (NHC), amine and carboxylate
donor groups coupled to benzothiazole- or stilbene-based amyloid binding moieties were synthesised.
Reaction of the imidazolium salt containing pro-ligands with Re(CO)5Cl yielded the corresponding
rhenium metal complexes which were characterised by NMR, and X-ray crystallography. These
ligands are of interest for the potential preparation of technetium-99m imaging agents for Alzheimer’s
disease and the capacity of these rhenium complexes bind to amyloid fibrils composed of amyloid-β
peptide and amyloid plaques in human frontal cortex brain tissue was evaluated using fluorescence
microscopy. These studies show that the complexes bound efficiently to amyloid-β fibrils and some
evidence of binding to amyloid-β plaques.
Introduction
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterised by severe
memory loss and disturbances in cognitive and behavioural functions.1 The pathological mechanism
of AD remains unknown, however the formation of insoluble plaques in the brain composed of the
amyloid-β peptide are believed to play an important role in the progression of this disease.2 Therefore,
evaluation and quantification of the amyloid-β plaque load using targeted radiopharmaceutical
diagnostic agents offer the potential for the early diagnosis of AD.3
Positron emission tomography (PET) and single photon emission computed tomography
(SPECT) are the two most common nuclear imaging techniques that use radioactive tracers to
diagnose diseases.4 These techniques allow for the non-invasive visualisation of disease progression
at various levels ranging from molecular to whole organ.5 PET radiotracers require positron emitting
radionuclides such as 11C (t1/2 = 20.3 mins) and 18F (t1/2 = 109.8 mins), whereas SPECT radiotracers

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require gamma emitting radionuclides such as 99mTc (t1/2 = 6.06 hours) and 123I (t1/2 = 13.2 hours).6, 7
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DOI: 10.1039/C9DT04687A
Even though SPECT has a lower sensitivity and resolution compared to PET, it is widely available
in many hospitals and for the commonly used isotope 99mTc there is no requirement for an onsite
cyclotron.8, 9 Therefore, the development of SPECT radiotracers labelled with 99mTc for the diagnosis
AD offers the potential for an easily accessible and affordable nuclear medicine technique for the
early detection of this disease.10-12
Metal complexes of N-heterocyclic carbene (NHC) ligands have been extensively studied for
a range of applications, including as homogeneous chemical catalysts,13 luminescent and
electroluminescent materials14 and as potential medicinal agents.15 Despite their outstanding
properties as ligands, less work has been directed towards the use of NHCs for the development of
diagnostic imaging agents based on metallic radionuclides. We are interested in the preparation of
new NHC ligands for radiopharmaceutical applications and previously we reported the first example
of labelling an NHC ligand with the 99mTc (in the form of 99mTc(CO)3).16 As part of this research, we
have studied the chemistry of the Re(CO)3 core with bidentate and tridentate NHC ligands.16, 17 Che
and co-workers reported early examples of Re(CO)3 complexes of NHC ligands e.g. I,18 while more
recently, Re(CO)3 complexes with bidentate pyridyl-, quinolinyl- and pyrimidyl-functionalized NHC
ligands e.g. II, and III and IVhave been described (Figure 1).19, 20
+
R
NH
NH
N
N
N
N
N
Ph
N
nBu
OC
N
N
N
R
OC
OC
OC
OC
N
X
N
X
Re
OC
N
X
Re
OC
Re
OC
Re
OC
OC
OC
R
OC
Br-
II
III
I
IV
Figure 1. Examples of Re(CO)3 complexes with N-heterocyclic carbene ligands.
Previously we reported a series of Re(CO)3 complexes of bifunctional bis(NHC)-amine
ligands coupled to benzothiazole- V and stilbene-based VI amyloid binding moieties (Figure 2).21
These complexes were highly stable in ligand challenge experiments with histidine and cysteine and
bound to amyloid fibrils composed of the amyloid-β peptide. In addition, epi-fluorescence
microscopy studies showed that VI bound selectively to amyloid plaques in human Alzheimer’s
disease brain tissue.21 Despite these promising results, complexes of this type are unlikely to be useful
for radiopharmaceutical applications as the cationic charge associated with complex VI is likely to
impede its passage through the blood brain barrier.22

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H
N
H
+
+
O
N
O
N
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DOI: 10.1039/C9DT04687A
S
N
N
N
N
N
N
CO
CO
CO
N
N
Re
N
N
N
Re
N
CO
-
-
PF6
CO
PF6
CO
V
VI
Figure 2. Structures of Re complexes of cyclic bis(NHC)-amine ligands coupled to benzothiazole- V
and (b) stilbene-based VI amyloid binding moieties.
In an effort to improve the potential application of N-heterocyclic carbene ligand of the
Re(CO)3 /Tc(CO)3 core for radiopharmaceutical applications, the synthesis of a new series of
tridentate ligands that combine a NHC unit with amine and carboxylate donors to produce neutral
complexes with the M(CO)3 core are reported herein. These ligands have been coupled to
benzothiazole- and stilbene-based amyloid binding moieties and the capacity of the Re(CO)3
complexes to bind to amyloid fibrils and amyloid plaques in human frontal cortex brain tissue are
evaluated.
Result and Discussion
Ligand synthesis
A key goal of this work was the development of bifunctional tridentate N-heterocyclic carbene
pro-ligands that would form neutral complexes of the [Re(CO)3]+ core. To this end, the closely related
pro-ligands 7 (Scheme 1) and 10 (Scheme 3) were prepared. The synthetic pathway for the formation
of pro-ligand 7 began with the reductive amination of benzaldehyde with ethanolamine using sodium
borohydride (NaBH4) to produce 1 (Scheme 1). Compound 1 was then N-alkylated with t-butyl
bromoacetate to form 2 followed by removal of the amine benzyl-protecting group via catalytic
hydrogenolysis, yielding compound 3. The deprotected secondary amine of 3 was then N-alkylated
with benzyl bromoacetate to form 4, thereby introducing orthogonal t-butyl ester and benzyl ester
carboxylic acid protecting groups. The orthogonal protecting groups were introduced to allow
selective deprotection using either trifluroacetic acid (TFA) or via catalytic hydrogenolysis. The
primary alcohol unit of 4 was then converted to an alkyl bromide using triphenylphosphine and N-
bromosuccinimide to produce compound 5 and the alkylation of 1-methylimidazole with 5 produced
the imidazolium salt 6 (Scheme 1). Removal of the t-butyl ester group of 6 with TFA yielded
compound 7 with a free carboxylic acid group. Difficulties were encountered in the purification of 7
as the bromide salt and to overcome this issue, a metathesis reaction was performed to convert the
bromide anion to hexaflorophosphate. Thus, 7 was isolated in its pure form as the hexaflorophosphate

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salt, which displayed appropriate solubility in organic solvents for the coupling reaction (amide bond
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DOI: 10.1039/C9DT04687A
formation) to introduce the amyloid binding moiety.
OH
O
OH
N
O
OH
N
Br
N
H
O
O
H
H2, 10% Pd/C
CH3OH
O
NaHCO3, CH3CN
O
1
2
3
O
O
N
OH
O
O
Br
N
Br
O
O
O
O
PPh3
NBS, CH2Cl2
O
O
4
5
NaHCO3, DMF
+
+
N
N
N
N
O
N
HO
N
N
N
CH2Cl2, TFA
O
O
O
O
CH3CN, 100 °C
O
O
7
6
Br-
-
PF6
Scheme 1. Synthesis of pro-ligand 7 using the orthogonal protecting group strategy.
The
coupling
reagent
PyBop
((benzotriazol-1-yloxy)tripyrrolidinophosphonium
hexafluorophosphate) was used to couple the carboxylic acid group of the pro-ligand 7 and the amine
unit of the amyloid binding moiety 6-amino-2-(4-N,N-dimethylaminophenyl)benzothiazole (Scheme
2). PyBop was chosen for this reaction as the by-product phosphonium salt could be readily removed
from the product 8, by washing with diethyl ether and the final ligand 9 was obtained as a bright
yellow solid after catalytic hydrogenolysis to remove the benzyl ester protecting group (Scheme 2).
+
N
N
H
+
N
N
S
N
HO
N
N
N
N
PyBop, DIPEA, CH2Cl2
O
O
O
O
H2N
S
N
-
O
O
PF6
N
-
PF6
8
7
N
H
+
N
N
S
N
H2, 10% Pd/C
CH3OH, 50°C
N
N
O
O
-
OH
PF6
9
Scheme 2. Synthetic scheme for the formation of 9.

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In the case of pro-ligand 12, coupled to the stilbene-based amyloid binding moiety 4-amino-
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DOI: 10.1039/C9DT04687A
4'-(N,N-dimethylamino)stilbene (Scheme 3), catalytic hydrogenolysis was not suitable for unmasking
the final carboxylic acid group due to the potential for simultaneous reduction of the alkene group of
the stilbene unit. Therefore, the benzyl ester protecting group of 6 was first deprotected via catalytic
hydrogenolysis to generate 10 and the formed carboxylic acid group was then coupled to 4-amino-4'-
(N,N-dimethylamino)stilbene using PyBop yielding 11 (Scheme 3). The t-butyl ester group was then
removed in the final step using TFA producing pro-ligand 12.
+
+
O
N
H2N
O
N
O
O
N
N
H2, 10% Pd/C
CH3OH
Br-
N
O
O
N
OH
PyBop, DIPEA, CH2Cl2,
N
-
O
PF6
6
10
+
+
N
N
O
OH
CH2Cl2, TFA,
O
O
O
O
N
N
-
PF6
N
N
N
N
Cl-
H
H
N
N
11
12
Scheme 3. Synthetic pathway for the formation of the stilbene derivative 12.
Rhenium complex synthesis
A silver transmetalation protocol was utilised for the synthesis of rhenium tricarbonyl
complexes 13 and 14 from ligands 9 and 12 respectively (Scheme 4). The silver transmetalation
methodology utilisingAg2O has been commonly employed for the formation of metal complexes of
NHC ligands from precursor imidazolium salts,23, 24 and we have previously described the synthesis
of a range of NHC complexes of the Re(CO)3 core using this approach.16, 17, 21 In the present work,
complex 13 was prepared by stirring a suspension of 9 and Ag2O in acetonitrile for 24 h to allow the
Ag-NHC complex to form and then Re(CO)5Cl was added and the reaction mixture was stirred for a
further 24 h at 60 °C. After completion of the reaction, the desired complex was purified by column
chromatography on alumina and complex 13 was obtained as an orange solid (Scheme 4).

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H
N
O
N
H
S
N
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DOI: 10.1039/C9DT04687A
+
N
N
N
S
N
N
N
N
(1) Ag2O, CH3CN
(2) Re(CO)5Cl
O
O
N
CO
N
-
PF6
OH
Re
CO
O
CO
O
9
13
H
+
O
N
N
N
OH
N
CO
O
O
N
(1) Ag2O, CH3CN
(2) Re(CO)5Cl
N
Re
CO
O
N
N
Cl-
CO
O
H
N
N
14
12
.Cl
Scheme 4. Synthetic pathway for the formation of the Re complexes 13 and 14.
For the synthesis of the Re complex of pro-ligand 12, the same procedure as that described
for the preparation of 13 was initially investigated, however the desired compound could not be
isolated under these conditions, possibly due to slow formation of the intermediate Ag complex. To
facilitate formation of the Ag complex, a metathesis reaction was used to exchange the counterion of
12 from hexafluorophosphate to chloride yielding compound 12Cl which allowed for the successful
synthesis of the desired Re complex 14 (Scheme 4).
As expected, no signals corresponding to the carboxylic acid or the imidazolium C2 protons
of the pro-ligands were apparent in the 1H-NMR spectra of complexes 13 and 14, indicating that these
groups are deprotonated and coordinated to the Re metal centre. The amide N-H signals resonate as
downfield shifted singlets at 10.5 ppm and 10.3 ppm for 13 and 14 respectively (Figures S17 and
S18, ESI). The labelled 1H-NMR spectrum for 13 is shown in Figure 3. As the facially coordinated
tridentate ligands have three different donor groups (amine, carboxylate, and carbene) the Re metal
is a chiral centre for complexes 13 and 14, and the non-superimposable mirror image forms of core
structure for these complexes are shown in Figure 4. As a result of this chirality, the methylene
protons of the acetamide linker group (shown in red on Figure 4) are diastereotopic and resonate as
an AB pattern (highlighted in red in Figure 3). The 13C-NMR spectra of complexes 13 and 14 show
the expected number of peaks for the respective complexes (Figures S17 and S18, ESI). For each
complex, three individual signals corresponding to the carbonyl ligands are evident in the region of
198-196 ppm consistent with this group being trans to the three different donor groups of the
tridentate ligand.

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Figure 3. 1H-NMR spectrum of complex 13 (DMSO-d6) The signal corresponding to the methylene
group protons of the acetamide linker is highlighted in red.
O
H
O
H
R
R
N
N
H
H
N
N
N
N
CO
OC
Re
Re
O
O
CO
OC
O
O
CO
CO
Figure 4. Diagram showing the non-superimposable forms of the chiral complexes 13 and 14 (R =
amyloid binding moiety).
To explore the influence of the tridentate ligand on the carbonyl ligands, the solid-state IR
spectra for complexes 13 and 14 (Figures S19 and S20, ESI) were recorded. In each case, strong and
distinct CO stretching signals were observed at 2017 cm-1 and 2015 cm-1, while broad (apparently
overlapping as a result of solid-state effects25-27) signals were observed at 1890 cm-1 and 1886 cm-1
for complexes 13 and 14. These results are consistent with the expected three individual signals for
each of the carbonyl ligands which are either trans to the amine, carboxylate or carbene donor groups.
It is well known that the strong -donor properties of NHCs causes the signal for carbonyl ligand
trans to these groups to be shifted to higher wavenumbers and as such the signals observed at 2017
cm-1 and 2015 cm-1 for 13 and 14 respectively can be assigned to the carbonyl ligand trans to the
NHC donor.28
X-ray Structural Studies
The X-ray crystal structure for complex 14 and a poor-quality structure for 13 (included for
comparative purposes) are shown in Figure 5. The X-ray crystallographic data for these compounds
are given in Table S1 (ESI). In each case, the X-ray crystal structures confirm that the ligands are
coordinated to the Re metal centres as facial tridentates via the NHC, tertiary amine and carboxylate
groups, with the additional three coordination sited being occupied by carbonyl ligands. For

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compounds 13 and 14 respectively, the benzothiazole- and stilbene-based amyloid binding moieties
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DOI: 10.1039/C9DT04687A
are linked to the tertiary amine donor atom via an acetamide linkage. The Re−Ccarbene, Re−Namine and
Re−Ocarboxylate bond lengths (Figure 5 caption) are similar for each complex and the Re-Ccarbonyl bond
lengths lie within typical ranges (1.90-2.10 Å).18, 27, 29 As mentioned in the previous section, NHC
ligands are strong -donors and are well known to exert a strong trans influence. In the case of
compound 14, the trans influence exerted by the NHC ligand is apparent and the Re-carbonyl bond
length (Re-C(2) = 1.962(7) Å) is significantly longer than those for the two other carbonyl ligands
(Re-C(3) = 1.928(8) Å and Re-C(4) = 1.916(8) Å). In contrast, this effect is not observed in the
structure for 13, however this is possibly a result of the lower quality of this structure.
Figure 5. X-ray crystal structures of the Re complexes (a) 13 and (b) 14. Ellipsoids are shown 40%
probability. Selected bond lengths: 13 Re-O(1) = 2.124(19) Å, Re-N(3)=2.30(2) Å, Re-C(1) = 2.22(3)
Å, Re-C(2)=1.90(4) Å, Re-C(3) = 1.91(3) Å, Re-C(4)=1.90(3) Å and 14 Re-O(1) = 2.156(4) Å, Re-
N(3) = 2.273(5) Å, Re-C(1) = 2.164(7) Å, Re-C(2) = 1.962(7) Å, Re-C(3) = 1.928(8) Å, Re-C(4) =
1.916(8) Å.
Octanol-Water Partition Coefficient
The NHC ligand reported here were designed for the generation of neutral complexes with
either the [Re(CO)3]+ or [Tc(CO)3]+ cores for potential radiopharmaceutical applications. As
neuroimaging applications are of interest, neutral complexes were desired to achieve sufficient

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lipophilicity to modulate the blood brain barrier (BBB) permeability. Molecules are known to cross
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the blood-brain barrier (BBB) by several mechanisms, including passive diffusion or active transport.
Passive diffusion is the most common mechanism for drugs to cross the BBB and relies upon a
moderate to high degree of lipid solubility.30 To evaluate the lipid solubility of the Re complexes 13
and 14, the logP values were estimated using octanol-water partition coefficient experiments,
conducted using the slow stirring method.31 The results of these studies shown that complex 13 has
logP value of 0.15 ± 0.01, while complex 14 has a higher logP value of 0.39 ± 0.01. These logP
values of both are somewhat lower than the optimum range required for good BBB permeability, for
example Hansch and Leo found that BBB penetration is optimal when the logP values are in the range
of 1.5-2.7.32 However, with the development of this new synthetic approach for the preparation of
tridentate NHC pro-ligands, the introduction of more lipophilic groups (for example extended alkyl
chains on the NHC units) will be straightforward and allow for the ready modulation of logP values
for the resulting complexes.
Interaction of 13 and 14 with Amyloid-(1-40) and Amyloid-Plaques
The formation of amyloid-β (Aβ) fibrils from the Aβ(1-40) peptide in vitro can be monitored
using thioflavin-T (ThT) as the interaction between ThT and Aβ fibrils results in strong fluorescence
emission at 480 nm.33-38 The interaction between the Re complexes 13 and 14 and amyloid was
studied using a ThT-based fluorescence assay. The fluorescence emission at em = 480 nm for a
freshly prepared solution of Aβ1-40 (4 µM) and ThT (4 µM) at 37 ⁰C in the presence of each of the
complexes 13 and 14 was monitored over a period of 66 h but no change was observed after 10 h
(Figure 6). The control sample, where no complex was added, confirmed the formation of Aβ fibrils
as indicated by the increased fluorescence intensity for fibril-bound ThT at em = 480 nm. The
addition of either complex 13 or 14 resulted in a significantly reduced fluorescence suggesting that
Re complexes 13 and 14 either bind competitively with ThT to Aβ(1-40) fibrils or that the complexes
inhibit the formation of A(1-40) fibrils.

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Figure 6. Thioflavin T (ThT) fluorescence assay over a period of 25 h for solutions of ThT (4 µM)
and Aβ1-40 (4 µM) at 37 ⁰C in the presence of: no addition (control, black), 13 (red) and 14 (green) (1
µM in each case).
The capacities of the complexes to bind to amyloid plaques in human brain tissue were
investigated using epi-fluorescence microscopy. To facilitate these studies the electronic absorption
and emission spectra for the metal complexes 13 and 14 (together with the pro-ligands 9 and 12) were
recorded (Figures S23-S26, ESI) and for the complexes, the emission maxima occurred at  ~ 420
nm and  ~ 457 nm respectively. Frontal cortex brain tissue (7 µm sections) collected from post-
mortem subjects with clinically diagnosed AD was compared to tissue from an age-matched healthy
control following treatment with complex 13 or complex 14. The treated tissues were examined by
epi-fluorescence microscopy and then compared to contiguous sections that were immuno-stained
with an anti-amyloid-β(1-42) antibody (1E8) to identify Aβ plaques (Figure 7). The results of these
human brain staining studies showed evidence for moderate levels of co-localisation of complexes
13 and 14 with the amyloid-β plaques (Figure 7b and 7f). However, the epi-fluorescent images for
the age-matched controls showed no evidence of non-specific binding for both complexes. Although
the cause of the relatively low levels of co-localisation for these complexes with the amyloid plaques
is not known, it may be due to the relatively short linker group between the amyloid binding moiety
and the relatively large octahedral Re metal complexes.

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Figure 7. Epi-fluorescence microscopy images of frontal cortex brain tissue from AD patient treated
(a, b, e & f) and from healthy age-matched control (c, d, g & h). Images a, e, c & g were stained with
amyloid specific antibody (1E8) and visualised under brightfield. Images b & d were stained with 13
and f & h were stained with 14 and visualised using epi-fluorescence microscopy (λex = 405 nm, λem
= 460 nm)
Conclusion
In conclusion, two tridentate N-heterocyclic carbene pro-ligands bearing imidazolium, amine
and carboxylate donor groups coupled to either a benzothiazole- or a stilbene-based amyloid binding
moiety were designed and synthesised. These pro-ligands were then used to prepare two neutral NHC
complexes of the [Re(CO)3]+ core (13 and 14) and the logP values for these compounds were
determined to be 0.15 ± 0.01 and 0.39 ± 0.01 respectively. Studies using the histological dye
Thioflavin-T showed that these complexes bound to fibrils formed from the amyloid-(1-40) peptide.
Epi-fluorescence microscopy co-localisation studies for compounds 13 and 14 and the amyloid
specific antibody 1E8 in frontal cortex brain tissue from AD patient were consistent with the
complexes binding to amyloid- plaques at moderate to low levels. It is possible that the presence of
the octahedral metal complex and the relatively low lipophilicity of 13 and 14 reduced their ability to
bind to amyloid plaques. The new ligand systems reported here are promising for the development of
NHC based imaging agents as they form neutral and stable complexes with the [Re(CO)3]+ core. The
logP values for the Re complexes (13 and 14) are not within the optimum range for CNS penetration,
however the structures of the synthesised pro-ligands offer the potential to be modified to increase
the lipophilicity. For example, the NHC unit has a methyl substituent and this could be modified to a
more lipophilic component e.g. tert-butyl or cyclohexyl in a relatively straightforward manner.
Currently we are undertaking studies into the preparation of the corresponding 99mTc(CO)3 complexes
of these ligands and these resulted will be communicated in due course.

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Experimental details
General procedures: All reagents were purchased from Sigma Aldrich or Alfa Aesar and were used
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DOI: 10.1039/C9DT04687A
without
further
purification
unless
otherwise
stated.
6-amino-2-(4-N,N-
40
dimethylaminophenyl)benzothiazole39 and 4-amino-4'-(N,N-dimethylamino)stilbene29,
were
synthesised as described previously. NMR spectra were recorded on either a Bruker Avance ARX-
400 (400.13 MHz for 1H, 100.61 MHz for 13C), or a Bruker Avance ARX-500 (500.13 MHz for 1H,
125.77 MHz for 13C) spectrometer and were internally referenced to solvent resonances. High
resolution mass spectra were obtained using an Agilent 6530 QTOF LC/MS mass spectrometer fitted
with an Agilent electrospray ion (ESI) source. UV-visible spectra were recorded using an Agilent
Technologies Cary 300 UV-visible spectrophotometer using quartz cuvettes (1 cm). Fluorescence
spectra were recorded on a Varian Cary Eclipse spectrofluorimeter (5 nm bandpass, 1 nm data
interval, PMT voltage: 600 V) using quartz cuvettes (1 cm). Infra-red spectra were recorded using an
Agilent Cary 660 FT-IR spectrophotometer in ATR mode.
X-ray Crystallography. Single crystals of complexes 13 and 14 suitable for X-ray diffraction studies
were grown by slow evaporation in dichloromethane solutions of these complexes. Crystallographic
data for all structures determined are given in Table S1 (Supporting Information). For all samples,
crystals were removed from the crystallisation vial and immediately coated with Paratone oil on a
glass slide. A suitable crystal was mounted in Paratone oil on a glass fiber and cooled rapidly to
150K (13) or 136K (14) in a stream of cold N2 using an Oxford low-temperature device. Diffraction
data were measured using an Oxford Gemini diffractometer mounted with Mo-Kα  = 0.71073 Å and
Cu-Kα  = 1.54184 Å. Data were reduced and corrected for absorption using the CrysAlis Pro
program.41 The SHELXL2013-242 program was used to solve the structures with Direct Methods,
with refinement by the Full-Matrix Least-Squares refinement techniques on F2. The non-hydrogen
atoms were refined anisotropically and hydrogen atoms were placed geometrically and refined using
the riding model. Coordinates and anisotropic thermal parameters of all non-hydrogen atoms were
refined. All calculations were carried out using the program Olex2.43 Further XRD details are
provided in the Electronic Supplementary Information. CCDC 1969630-1969631 contains the
supplementary crystallographic data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/structures/
ThT Fluorescence Aβ binding Assays. Synthetic Aβ1-40 (500 µg, Bachem, 4014442) was dissolved
in HFIP (500 μL) then incubated on ice for 1 hour. The solution was then allowed to evaporate
overnight followed by drying by high speed vacuum centrifugation to remove residual HFIP and
moisture. The peptide was dissolved in 60 mM NaOH (100 μL) and incubated for 3 min at room

Page 13 of 20
Dalton Transactions
temperature then MilliQ water (350 μL) was added and the solution was vortex briefly followed by
View Article Online
DOI: 10.1039/C9DT04687A
ultrasoniacation for 5 minutes on ice. 10 × PBS (pH 7.4, 50 μL) was added to the solution then
vortexed briefly and centrifuged for 5 min. Supernatant was transferred to a fresh tube and kept on
ice. The concentration of the Aβ1-40 solution was determined by its absorbance at 214 nm (ε = 94526
M-1 cm -1) and found to be 148 µM. Stock solutions of ThT (1 mM in PBS), complexes 13 and 14 (1
mM in DMSO) were prepared freshly and final samples were prepared on ice by mixing Aβ1-40 (final
concentration: 4 µM), ThT (final concentration, 4 µM) and the chosen Re complex (final
concentration: 1 µM), and the control consisting of Aβ1-40 (final concentration: 4 µM) and ThT (final
concentration: 4 µM). All samples were prepared in triplicates and the ThT fluorescence intensity of
each sample was recorded every 10 min at 37 ⁰C using a FLUOstar Omega filter-based multi-mode
microplate reader with 440/480 nm excitation/emission filters over a period of 66 h with orbital
shaking before each cycle.
Staining of Human AD Brain Tissues. The Health Sciences Human Ethics Sub-committee, The
University of Melbourne, approved all experiments using human brain tissue (Ethics Approval No.
1341145). Brain tissue was collected at autopsy. Brain tissue from the frontal cortex was preserved
by formalin fixation and paraffin embedding. AD pathology was confirmed according to standard
National Institute of Aging and Reagan Institute Working Group on Diagnostic Criteria for the
Neuropathological Assessment of Alzheimer's Disease (1997) criteria. The brain tissue samples of
age-matched Human controls (HC) were subject to the above criteria. The AD and HC brain tissue
sections (7 µm) were first deparaffined (xylene, 3 × 2 min) followed by rehydration (soaking for 2
min in a series of 100%, 90%, 70%, and 0% v/v ethanol/water). The hydrated tissue sections were
washed in phosphate buffer saline (PBS, 5 min). Autofluorescence of the tissue was quenched using
potassium permanganate (KMnO4) (0.25% in PBS, 20 min) and the sections were further washed
with PBS (2 × 2 min) to remove the excess KMnO4. The brown-coloured sections were washed with
potassium metabisulfite and oxalic acid (1% in PBS) until the brown colour was removed followed
by washing with PBS (3 × 2 min). The sections were blocked with bovine serum albumin (2% BSA
in PBS, pH 7.0, 10 min) and covered with a solution of the chosen Re complex (10 μM in 15% v/v
DMSO/PBS, 10 min). The sections were treated with BSA again (4 min) to remove any Re complex
non-specifically bound to the tissue. Finally, the sections were washed with PBS (3 × 2 min), DI
water, and mounted with a DAKO fluorescence mounting medium Fluorescence images were
visualized using a Leica DM IL LED microscope.
Partition coefficient (LogP) studies. 1-Octanol/water partition coefficients for complexes 13 and 14
were determined using the slow-stirring method as described by Pereiro and co-workers.31 The 1-
octanol and Mili-Q water were saturated prior their use and the starting concentration of complexes

Dalton Transactions
Page 14 of 20
13 and 14 in the 1-octanol phase was 80 µM. Approximately 5 mL of the pre-saturated water and 1-
View Article Online
DOI: 10.1039/C9DT04687A
octanol were added to a glass vial containing a magnetic stir bar. The vials were slowly stirred and
maintained at 25 ⁰C for two days. The metal complex concentration in the 1-octanol phase was then
analysed using an Agilent Technologies Cary 300 UV-visible spectrophotometer in a quartz cuvette
(1 cm). A calibration curve for each complex was prepared at its max value (365 nm for 13 and 360
nm for 14).
Synthesis
6: A solution of 1-methylimidazole (0.12 g, 1.51 mmol) in acetonitrile (10 mL) was added dropwise
to a solution of 5 (0.58 g, 1.51 mmol) in acetonitrile (40 mL) and the mixture was refluxed at 100 C
overnight. After removal of solvent on a rotatory evaporator, the crude product was purified on silica
with methanol (2%) and dichloromethane (98%) as the eluent and the pure product was obtained as
1
a yellow oil. (Yield: 0.47 g, 81%). H NMR (400 MHz) (CDCl ): (ppm) 1.42 (s, 9H, CH ), 3.18
훿
3
3
(m, 2H, CH2), 3.39 (s, 2H, CH2), 3.56 (s, 2H, CH2), 3.99 (s, 3H, CH3imi), 4.43 (m, 2H, CH2), 7.26 (t,
1H, 3JH-H = 1.76 Hz, Himi), 7.31-7.36 (m, 5H, HAr), 7.88 (t, 1H, 3JH-H = 1.72 Hz, Himi), 10.0 (s, 1H,
NCHN). 13C NMR (CDCl ): (ppm) 36.5 CH3imi, 48.2 CH2, 50.6 Cq, 55.0 NCH2, 56.1 NCH2, 56.7
훿
3
NCH2, 66.7 O CH2-Ar, 81.9 Cq, 122.0 Cimi, 123.6 Cimi, 128.3 CAr, 128.5 CAr 128.7 CAr, 135.3 Cq,
138.0 Cimi, 170.3 Cq, 171.1 Cq. HRESI-MS+ (CH3OH): [C21H30N3O4]+ m/z = 388.2257, calcd =
388.2236.
7: To a stirred solution of 6 (0.40 g, 1.03 mmol) in dichloromethane (15 mL) at 0 ⁰C was added
dropwise a solution of trifluroacetic acid (2.55 g, 22.3 mmol) in dichloromethane (5 mL). The mixture
was then stirred at room temperature overnight. After removal of the solvent on a rotatory evaporator,
a yellow oil was obtained, which was dissolved in water (20 mL) and a saturated solution of KPF6
(1.33 g, 7.22 mmol) in water (20 mL) was added dropwise resulting in the formation of a white
precipitate. The mixture was extracted with dichloromethane (3
20 mL) and the combined organic
×
extracts were dried with MgSO4. The solvent was removed on a rotatory evaporator yielding the pure
compound as a colourless oil. (Yield: 0.47 g, 44%).1H NMR (500 MHz) (DMSO-d ): (ppm) 3.05
훿
6
(t, 2H, 3JH-H = 5.48 Hz, CH2), 3.45 (s, 2H, NCH2), 3.61 (s, 2H, NCH2), 3.81 (s, 3H, CH3), 4.21 (t, 2H,
CH2), 5.10 (s, 2H, CH2benzyl), 7.34-7.39 (m, 5H, HAr), 7.63 (t, 1H, 3JH-H = 1.64 Hz, Himi), 7.71 (t, 1H,
3JH-H = 1.68 Hz, H ), 9.05 (s, 1H, NCHN ). 13C NMR (DMSO-d ): (ppm) 36.1 CH , 47.6 CH ,
훿
imi
imi
6
3
2
53.9 CH2, 54.0 NCH2, 55.0 NCH2, 66.1 O-CH2-Ar, 123.2 Cimi, 123.3 Cimi, 128.5 CAr, 128.6 CAr, 128.9
CAr, 136.4 Cq, 137.5 Cimi, 171.4 C=O, 172.9 C=O. HRESI-MS+ (CH3OH): [C17H22N3O4]+ m/z =
332.1607, calcd = 332.1610.

Page 15 of 20
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT04687A
8: A mixture of 7 (0.32 g, 0.67 mmol), DIPEA (0.24 g, 1.83 mmol), PyBop (0.32 g, 0.670 mmol) and
6-amino-2-(4-N,N-dimethylaminophenyl)benzothiazole (0.16 g, 0.670 mmol) in dichloromethane (20
mL) was stirred at room temperature overnight. The solvent was removed using a rotary evaporator
and the crude product was washed with diethyl ether (3  10 mL) and a minimal amount of
1
dichloromethane to yield the pure product as a yellow solid. (Yield: 0.26 g, 40%). H NMR (400
3
MHz) (DMSO-d ): (ppm) 3.02 (s, 6H, CH ), 3.17 (t, 2H, J
= 5.16 Hz, CH2), 3.57 (s, 2H,
훿
6
3
H-H
NCH2O), 3.72 (s, 2H, NCH2), 3.76 (s, 3H, CH3imi), 4.28 (t, 2H, 3JH-H = 5.28 Hz, CH2), 5.15 (s, 2H,
CH2), 6.82 (d, 2H, 3JH-H = 9.00 Hz, HAr), 7.34-7.39 (m, 5H, HAr), 7.61 (s, 1H, HAr), 7.78 (d, 1H, 3JH-H
= 1.56 Hz, Himi), 7.84 -7.87 (m, 3H, HAr), 8.36 (d, 1H, 3JH-H = 1.92 Hz, Himi), 9.12 (s, 1H, Himi), 9.91
(s, 1H, NH). 13C NMR (DMSO-d ): (ppm) 36.1 CH3imi, 39.5-40.5 CH3, 47.6 CH2, 54.4 CH2, 55.5
훿
6
NCH2, 58.3 NCH2, 66.2 O-CH2-Ar, 111.9 Cimi, 112.3 CAr, 119.0 Cq,120.7 CAr, 122.3 CAr, 123.2 Cimi,
123.5 CAr, 128.5-128.9 Cbenzothiazole, 134.8 Cq, 135.9 Cq, 136.3 Cq, 137.5 Cimi, 150.6 Cq, 152.6 Cq,
167.1 Cq, 169.6 Cq, 171.8 Cq. HRESI-MS+ (CH3OH): [C32H35N6O3S]+ m/z = 583.2516, calcd =
583.2491.
9: To a solution of 8 (0.21 g, 0.30 mmol) in hot methanol (50 mL) was added 10% Pd/C (0.05 g) and
the mixture was heated at 40 C under an atmosphere of hydrogen for 5 h. The reaction mixture was
filtrated through a plug of Celite, and after removal of the solvent on a rotatory evaporator the product
1
was obtained as a bright yellow solid. (Yield: 0.18 g, 82%). H NMR (400 MHz) (DMSO-d ):
훿
6
(ppm) 3.02 (s, 6H, CH3), 3.16 (t, 2H, 3JH-H = 5.48, NCH2), 3.54 (s, 2H, NCH2), 3.54 (s, 2H, NCH2),
3.77 (s, 3H, NCH3), 4.26 (t, 2H, 3JH-H = 5.36, CH2), 6.82 (d, 2H, 3JH-H = 8.92, HAr, 7.45-7.47 (dd,
1H, HAr), 7.62 (s, 1H, HAr), 7.79 (s, 1H, Himi), 7.85 (d, 2H, HAr), 7.87 (d, 1H, HAr), 8.37 (d, 1H, 3JH-H
= 1.80 Hz, H ), 9.14 (s, 1H, H ). 13C NMR (DMSO-d ): (ppm) 36.1 CH3imi, 39.5-40.5 CH3, 47.6
훿
imi
imi
6
CH2, 55.7 NCH2, 58.6 NCH2, 111.8 Cimi, 112.3 CAr, 118.9 CAr, 120.7 Cq, 122.3 CAr, 123.2 Cimi, 123.5
CAr, 128.7 CAr, 134.9 Cq, 135.9 Cq, 137.5 Cimi, 150.5 Cq, 152.6 Cq, 167.1 Cq, 169.9 Cq, 173.7 Cq.
HRESI-MS+ (CH3OH): [C25H29N6O3S]+ m/z = 493.1995, calcd = 493.2022.
10: To a stirred solution of 6 (5.50 g, 11.7 mmol) in methanol (70 mL), 10% Pd/C (0.50 g) was added
and the reaction was stirred under an atmosphere of hydrogen overnight. The mixture was filtered
through a plug of Celite and the solvent was removed on a rotatory evaporator yielding a yellow oil.
The yellow oil was dissolved in water (10 mL) and a solution of KPF6 (1.01 g, 5.51 mmol) in water
(10 mL) was added dropwise, resulting in the formation of a white precipitate. The mixture was
extracted with dichloromethane (3
10 mL) and the combined organic extracts were dried with
×
MgSO4 and the solvent was removed on a rotatory evaporator yielding the pure compound as yellow

Dalton Transactions
Page 16 of 20
oil. (Yield: 0.45 g, 38%). 1H NMR (400 MHz) (DMSO-d ): (ppm) 1.40 (s, 9H, CH ), 3.03 (t, 2H,
훿
6
3
View Article Online
3
JH-H = 5.64 Hz, CH2), 3.41 (s, 2H, NCH2), 3.43 (s, 2H, NCH2), 4.21 (t, 2H, 3JH-H = 5.36 Hz, CH2),
DOI: 10.1039/C9DT04687A
7.67 (s, 1H, H ), 7.75 (s, 1H, H ), 9.08 (s, 1H, H ). 13C NMR (DMSO-d ): (ppm) 28.3 CH ,
훿
imi
imi
imi
6
3
36.1 CH3imi, 47.6 CH2, 54.0 CH2, 55.0 NCH2, 55.8 NCH2, 80.9 Cq, 123.2 Cimi, 123.2 Cimi, 137.5 Cimi,
170.7 C=O, 172.9 C=O. HRESI-MS+ (CH3OH): [C14H24N3O4]+ m/z = 298.1766, calcd = 298.1767.
11: The compound was prepared as described for 9 from 10 (0.20 g, 0.43 mmol), DIPEA (0.17 g,
1.30 mmol), PyBop (0.23 g, 0.43 mmol), 4-amino-4'-(N,N-dimethylamino)stilbene (0.10 g, 0.42
mmol). (Yield: 0.05 g, 17%). 1H NMR (400 MHz) (DMSO-d ): (ppm) 1.43 (s, 9H, CH3t-butyl), 2.93
훿
6
(s, 6H, CH3stilbene), 3.13 (t, 2H, 3JH-H = 5.75 Hz, CH2), 3.48 (s, 4H, NCH2), 3.78 (s, 3H, CH3imi), 4.25
3
3
3
(t, 2H, JH-H = 5.70 Hz, CH2), 6.71 (d, 2H, JH-H = 8.85 Hz, HAr), 6.91 (d, 1H, JH-H = 16.4 Hz,
CH=CH), 7.03 (d, 1H, 3JH-H = 16.5 Hz, CH=CH), 7.40 (d, 2H, 3JH-H = 8.80 Hz, HAr), 7.47 (d, 2H,
3JH-H = 8.70 Hz, HAr), 7.52 (d, 2H, 3JH-H = 8.60 Hz, HAr), 7.64 (s, 1H, Himi), 7.78 (s, 1H, Himi), 9.10
(s, 1H, H ), 9.72 (s, 1H, NH). 13C NMR (DMSO-d ): (ppm) 28.3 CH3t-butyl, 36.1 CH3imi, 39.5
훿
imi
6
CH3stilbene, 47.6 CH2, 54.5 CH2, 56.4 NCH2, 58.3 NCH2, 81.3 Ct-butyl, 112.8 CAr, 119.6 CAr, 123.2 Cimi,
123.5 Cimi, 123.6 CAr, 125.6 CAr, 126.7 CAr, 127.8 CAr, 128.0 Cq, 133.6 Cq, 137.5 Cimi, 137.7 Cq, 150.3
Cq, 169.5 C=O, 171.2 C=O. HRESI-MS+ (CH3OH): [C30H40N5O3]+ m/z = 518.3162, calcd = 518.310.
12: To a stirred solution of 11 (0.28 g, 0.42 mmol) in dichloromethane (15 mL) at 0 ⁰C was added
dropwise a solution of trifluroacetic acid (2.37 g, 20.8 mmol) in dichloromethane (5 mL) and the
mixture was stirred at room temperature overnight. The solvent was removed on a rotatory evaporator
yielding a yellow solid, which was dissolved in water (20 mL), the pH was then adjusted to 12 with
1M NaOH and the solution washed with dichloromethane (3
10 mL). The pH of the solution was
×
then adjusted to pH 7 using concentrated hydrochloric acid and the water was removed using rotatory
evaporator to obtain a yellow solid. The yellow solid (0.44 g) was redissolved in acetonitrile and a
solution of Bu4NCl (0.26 g, 0.95 mmol) in acetonitrile was added dropwise and the yellow precipitate
was collected via centrifugation. The solvent was removed on a rotatory evaporator yielding the pure
compound as a yellow solid. (Yield: 0.21 g, 57%). 1H-NMR (500 MHz) (DMSO-d ): (ppm) 2.92
훿
6
(s, 6H, CH3stilbene), 3.11 (t, 2H, 3JH-H = 5.50 Hz, CH2), 3.16 (s, 4H, CH2), 3.65 (s, 3H, CH3imi), 4.21
(s, 2H, CH2), 6.70 (d, 2H, 3JH-H = 9.15 Hz, HAr), 6.90 (d, 1H, 3JH-H = 16.4 Hz, CH=CH), 7.01 (d, 1H,
3
3
3JH-H = 16.4 Hz, CH=CH), 7.39 (d, 2H, JH-H = 8.80 Hz, HAr), 7.44 (d, 2H, JH-H = 8.60 Hz, HAr),
7.54 (s, 1H, Himi), 7.65 (d, 2H, 3JH-H = 8.40 Hz, HAr), 7.83 (s, 1H, Himi), 9.83 (s, 1H, Himi). 13C NMR
(DMSO-d ): (ppm) 35.9 CH3imi, 39.5 CH3stilbene, 47.8 CH2, 56.4 CH2, 58.1 CH2, 61.7 CH2, 65.4 Cq,
훿
6
112.8 CAr,119.6 CAr, 123.0 Cimi, 123.4 Cimi, 123.9 CH=CH, 125.7 Cq, 126.5 CAr, 127.6 Cq, 127.7 CAr,

Page 17 of 20
Dalton Transactions
133.1 Cq, 138.0 Cimi, 150.3 Cq, 171.3 Cq. HRESI-MS+ (CH3OH): [C26H32N5O3]+ m/z = 462.2512,
View Article Online
DOI: 10.1039/C9DT04687A
calcd = 462.2505.
13: A mixture of 9 (0.043 g, 0.069 mmol) and Ag2O (0.032 g, 0.14 mmol) in acetonitrile (25 mL)
was stirred at 60 C for 24 h. Re(CO)5Cl (0.025 g, 0.069 mmol) was then added and the mixture was
stirred at 60 C for a further 24 h. The mixture was filtered through Celite and the solvent was
removed from the filtrate on a rotatory evaporator yielding a yellow/brown solid. The yellow/brown
solid was dissolved in minimal amount of acetonitrile and purified on alumina using methanol (5%)
and dicholoromethane (95%) as the eluent. The product was obtained as yellow solid. (Yield: 0.020
g, 32%). 1H-NMR (500 MHz) (DMSO-d ): (ppm) 3.02 (s, 6H, CH ), 3.32-3.33 (m, 1H, CH ), 3.50-
훿
6
3
2
3.55 (m, 1H, CH2), 3.83 (d, 1H, 3JH-H = 16.4 Hz, CH2COO), 3.90 (s, 3H, CH3imi), 4.04-4.09 (m, 1H,
CH2), 4.16 (d, 1H, 3JH-H = 16.3 Hz, CH2COO), 4.22-4.26 (m, 1H, CH2), 4.31 (d, 2H, A3JH-H = 15.8
Hz, B3JH-H = 15.8 Hz, CH2CONH), 6.82 (d, 2H, 3JH-H = 9.15 Hz, HAr), 7.40 (d, 1H, 3JH-H = 1.75 Hz,
Himi), 7.46 (d, 1H, 3JH-H = 1.80 Hz, Himi), 7.51 (dd, 1H, 3JH-H = 2.15, 6.65 Hz, HAr), 7.84-7.88 (m,
3
13
3H, HAr), 8.43 (d, 1H, JH-H = 2.05, H ), 10.5 (s, 1H, NH). C NMR (DMSO-d ): (ppm) 39.0
훿
Ar
6
CH3imi, 39.5-40.5 CH3, 47.1 CH2, 59.8 CH2, 65.1 CH2, 69.4 CH2, 112.3 Cimi, 119.4 CAr, 122.4 CAr,
123.1 CAr, 123.2 Cimi, 128.8 CAr, 134.9 Cq, 135.6 Cq, 150.8 Cq, 152.6 Cq, 162.8 Cq, 166.8 Cq, 167.4
Cq, 178.5 Cq, 180.1 Cq, 196.2 Re-CO, 197.4 Re-CO, 197.7 Re-CO. HRESI-MS+ (CH3OH):
[C28H28N6O6ReSNa]+ m/z = 785.1170, calcd = 785.1168.
14: The compound was prepared as described for 13 from 12 (0.043 g, 0.069 mmol), Ag2O (0.032 g,
0.14 mmol) and Re(CO)5Cl (0.025 g, 0.069 mmol) in 1:9 dichloromethane and methanol (25 mL).
The product was obtained as yellow solid. (Yield: 0.030 g, 38%). 1H-NMR (500 MHz) (DMSO-d6):
(ppm) 2.93 (s, 6H, CH3stilbene), 3.32-3.33 (m, 1H, CH2), 3.46-3.51 (m, 1H, CH2), 3.80 (d, 1H, 3JH-H
훿
3
= 16.5 Hz, CH2COO), 3.90 (s, 3H, CH3imi), 4.03-4.08 (m, 1H, CH2), 4.14 (d, 1H, JH-H = 16.0 Hz,
3
CH2COO), 4.21-4.24 (m, 1H, CH2), 4.25-4.31 (m, 2H, CH2CONH), 6.72 (d, 2H, JH-H = 8.50 Hz,
HAr), 6.92 (d, 1H, 3JH-H = 16.0 Hz, CH=CH), 7.05 (d, 1H, 3JH-H = 16.0 Hz, CH=CH), 7.39-7.41 (m,
3H, HAr), 7.43 (d, 1H, 3JH-H = 1.50 Hz, Himi), 7.49 (d, 2H, 3JH-H = 9.00 Hz, HAr), 7.57 (d, 2H, 3JH-H
= 8.50 Hz, H ), 10.3 (s, 1H, NH). 13C NMR (DMSO-d ): (ppm) 39.0 CH3imi, 39.5-40.5 CH3stilbene
,
훿
Ar
6
47.1 CH2CH2, 59.8 CH2CH2, 65.1 CH2COO, 69.4 CH2COO, 112.7 CAr, 120.1 CAr, 123.1 Cimi, 123.2
Cimi, 123.6 CH=CH, 125.6 CArq, 126.7 CAr, 127.8 CAr, 128.2 CH=CH, 134.0 CArq, 137.4 CArq, 150.4
CArq, 166.5 CONH, 178.5 COO, 180.2 NCN, 196.2 Re-CO, 197.4 Re-CO, 197.7 Re-CO. HRESI-MS+
(CH3OH): [C29H31N5O6ReNa]+ m/z = 754.1590, calcd = 754.1651.

Dalton Transactions
Page 18 of 20
Electronic Supplementary Information
Synthesis of 6-nitro-2-(4-N,N-dimethylaminophenyl)benzothiazole,
dimethylaminophenyl)benzothiazole, p-nitro-p’-N,N-dimethylaminostilbene,
View Article Online
DOI: 10.1039/C9DT04687A
6-amino-2-(4-N,N-
p-amino-p’N,N-
dimethylaminostilbene and compounds 1-5. Additional X-ray crystallographic details, UV-vis and
emission spectra for 9, 12-14. Partition coefficient study details and NMR spectra for all prepared
compounds. IR spectra for 13 and 14.
Acknowledgements
We wish to acknowledge the Victorian Brain Bank Network for provision of human brain tissue.
Conflicts of interest
There are no conflicts of interest to declare
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